P907: CARFILZOMIB, DEXAMETHASONE, AND DARATUMUMAB (KDD) VS CARFILZOMIB AND DEXAMETHASONE (KD) IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM): FRAILTY SUBGROUP ANALYSIS OF THE CANDOR STUDY
Authors: H. Quach, X. Leleu, M.-V. Mateos, S. Z. Usmani, A. K. Nooka, A. Goldrick, R. Najdi, N. Shu, T. Facon
Journal: HemaSphere (2022)

Background: Frailty scores based on age, comorbidities, and functional status can help identify frail patients (pts) at risk of higher rates of treatment-related toxicity or poor outcomes. An analysis of carfilzomib-treated pts in ASPIRE, ENDEAVOR, and ARROW found that efficacy and safety of carfilzomib regimens is consistent regardless of frailty status (Facon Blood Adv 2020). Aims: To compare efficacy and safety across frailty subgroups in pts with RRMM treated with KdD vs Kd in the phase 3 CANDOR study. Methods: This post hoc analysis used a planned interim readout (June 15, 2020) of CANDOR (NCT03158688). Pts were categorized as fit, intermediate (int), or frail based on a frailty score of 0, 1, or ≥2. Scoring used an algorithm based on the International Myeloma Working Group (IMWG) frailty index: the final score is based on age (0 if ≤75 years, 1 if 76-80 years, 2 if >80 years), modified Charlson Comorbidity Index (CCI [Facon Blood Adv 2020]) (0 if CCI ≤1, 1 if CCI >1), and Eastern Cooperative Oncology Group performance status (ECOG PS) (0 if ECOG PS=0, 1 if ECOG PS=1, and 2 if ECOG PS=2). Progression-free survival (PFS) was summarized descriptively, with hazard ratio (HR) and 95% CI estimated by stratified Cox proportional hazards model. Overall response rate (ORR) was summarized descriptively, with odds ratio (OR) and 95% CI estimated by Mantel-Haenszel method. Response and progression were assessed by the Onyx Response Computer Algorithm using IMWG criteria. Results: Frailty status was generally proportional between arms, with 27% and 35% classified as fit, 43% and 36% int, 25% and 27% frail, and 5% and 2% unknown for KdD and Kd, respectively. Although baseline characteristics of the overall population were generally balanced, more pts had prior transplant in the KdD vs Kd arm for int (65% vs 36%) and frail (41% vs 27%) subgroups, and in the frail subgroup fewer pts were lenalidomide exposed (37% vs 61%)/refractory (25% vs 46%) in the KdD vs Kd arm. Median duration of treatment for KdD vs Kd was 99 weeks (wks) vs 68 wks for fit pts, 82 wks vs 31 wks for int pts, and 51 wks vs 21 wks for frail pts. Median PFS in KdD vs Kd arms was not reached (NR) vs 17.6 months (HR 0.64, 95% CI 0.38–1.07) for fit, NR vs 11.1 months (HR 0.44, 95% CI 0.28–0.69) for int, and 18.5 vs 9.3 months (HR 0.66, 95% CI 0.38–1.14) for frail pts. ORR for KdD vs Kd arms was 89% vs 89% (OR 1.09, 95% CI 0.35–3.38) for fit pts, 87% vs 70% (OR 2.95, 95% CI 1.31–6.62) for int pts, and 75% vs 54% (OR 2.39, 95% CI 1.09–5.22) for frail pts (Figure). Any grade treatment-emergent adverse events (TEAEs) occurred in >95% of pts across arms and subgroups. Grade ≥3 TEAEs occurred in 87% (KdD) and 70% (Kd) of fit pts, 84% and 71% of int pts, and 91% and 90% of frail pts. Fatal TEAEs occurred in 4% and 2% of fit pts, 11% and 9% of int pts, and 16% and 8% of frail pts in the KdD and Kd arms. Carfilzomib was discontinued due to TEAEs in 25% vs 17% of fit pts, 22% vs 29% of int pts, and 35% vs 23% of frail pts. Among TEAEs of interest, acute renal failure occurred in 0 fit pts, 3% vs 14% of int pts, and 8% vs 5% of frail pts, and infusion reactions occurred in 16% vs 2% of fit pts, 13% vs 4% of int pts, and 14% vs 13% of frail pts in the KdD vs Kd arms (Table). Image:Summary/Conclusion: Consistent with previous findings of the efficacy and safety benefits of KdD, a PFS benefit with KdD vs Kd was observed across frailty subgroups, without increased toxicity. The clinically meaningful ORR benefit in the frail subgroup may help physicians evaluate treatment options in this challenging group.